There exists a well-recognized need for reliable, accurate, and inexpensive blood flow measurement techniques that allow the detection of blood flow abnormalities in both adults and children. This need exists because of the large number of deaths and physical disabilities arising from diseases of the heart and major blood vessels. For example, in 1982, the losses due to early death amounted to 2,100,000 years of potential life that were lost due to heart and peripheral vascular and cerebrovascular diseases before the age of 65 years old. This amounted to almost 46 percent of the deaths in the United States in 1982 being due to diseases affecting blood flow to the brain or the heart. With respect to infants, 28,300 infants died before reaching 28 days of age in 1982, many having intraventricular hemorrhage or perinatal asphyxia (lack of oxygen to the brain around the time of birth). In addition to deaths, a large portion of the surviving infants suffered mental retardation and neurological handicaps due to these two disease categories. These two types of diseases are caused by perturbations in blood flow.
There are two general types of methods for measuring blood flow in humans--invasive and non-invasive techniques. The invasive techniques, are in general: radioactive isotope injection, radioactive organ scanning, positron emission tomography, and angiography. Since these invasive methods involve the use of radioactivity and injection, in general, only one study is performed. The ability to measure blood flow non-invasively and repeatedly in humans would allow the screening of susceptible patients and interruption in the final outcomes of the previously mentioned disease processes. There are two types of non-invasive blood flow measurements: Doppler flow meter and plethysmography. The plethysmography method can only be used in term infants and involves compression of the neck veins and is therefore, rarely used since it can cause an increase of blood in the brain. In addition, this method is not practical for the screening of premature infants.
The Dopoler method is, therefore, the only non-invasive method of performing blood flow analysis and is the only one which can be repeated as necessary. In general, this method involves the transmission of an ultrasound signal through the skin to a blood vessel and the detection of the Doppler shift in the reflected ultrasound signal resulting from the movement of the red blood cells. The Doppler shifted ultrasound signal is then utilized to determine the velocity of the blood flow. This method for measuring the flow of blood is complicated by the fact that in a blood vessel, there are many sets of blood cells moving at different velocities. Each of these sets of blood cells gives rise to a frequency shift, and the resulting Doppler shifted output signal from the flow meter is the sum of the signals from all of the individual sets of cells. This resulting signal is a complex wave comprising a number of different waveforms.
In addition, the analysis of the Doppler shifted signal is complicated by the presence of noise. An example of noise that is present in the Doppler shifted signal is that due to the movement of the blood vessel wall. The wall of a blood vessel moves out during the systole and returns during the diastole portion of the cardiac cycle. It is known in the art to utilize low-frequency filters to reduce the amplitude of the wall movement signals resulting from the diastolic wall movements, but the higher-frequency systolic movements that result in high frequencies are not removed by the low-frequency filters. The latter frequencies cannot be removed since they fall well within the frequency range of the signals resulting from the movement of the red blood cells.
Another problem that arises in attempting to analyze and display the Doppler shifted signal is that the heart rate varies not only from person to person but within a given person over a relatively short period of time. This makes interpretation of the resulting data very difficult since the difference in the cardiac cycle must be included if a diagnosis is to be performed since the resulting display can have a different appearance. This variation from cardiac cycle to cardiac cycle also makes it difficult to perform an averaging over a number of cycles using prior art techniques.
Because of the complexity of the Doppler shifted signal, it is necessary to perform analog or digital analysis of these signals in order to present the information in a manner which is useful to medical personnel attempting to diagnose blood flow rate. At present, there are three major techniques that are utilized to analyze these signals: zero crossing method, phase lock loop (PLL) method, and spectral analysis utilizing Fourier analysis. The most common of these techniques is the zero crossing method. This method involves the utilization of a zero crossing detector on the output of a Doppler ultrasonic flow meter. The zero crossing method is described in detail in the paper by M. J. Lunt, "Accuracy and Limitations of the Ultrasonic Doppler Blood Velocity Meter and Zero Crossing Detector," Ultrasound in Medicine and Biology, Vol. 2, pp. 1-10, Pergamon Press, 1975, GB. The problems with the zero crossing method are that it approximates the mean velocity envelope only in steady-state laminar flow, thus potentially producing significant error in estimating pulsatile flow that exists in human blood vessels. In addition, the method is amplitude dependent, and high-frequency, low-amplitude signals such as blood vessel noise can cause significant waveform distortion. In addition, the resulting waveform from the zero crossing method is difficult to interpret because the output signal is neither proportional to the instantaneous mean nor to the instantaneous peak velocity of the blood flow.
The second method that has been utilized to analyze the Doppler shifted signal is the phase locked loop (PLL) technique. The basic idea behind the PLL technique is to lock a voltage controlled oscillator onto an input signal that is under measurement. A phase detector is used to indicate the relative phase (frequency) difference between the input signal and the output of the voltage controlled oscillator. This difference signal is low-pass filtered and applied back to the voltage controlled oscillator in order to control it. When used to analyze the Doppler shifted signal, the difference signal from the phase detector consists of positive and negative displacements about a center line corresponding to the zero Doppler shift. This techniques is described in greater detail in the article by A. Sainz, V. C. Roberts, and G. Pinardi, "Phase-Locked Loop Techniques Applied to Ultrasonic Doppler Signal Processing," Ultrasonics, Volume 14, pp. 128-132, 1976.
The problem with applying the PLL technique to a complex spectra such as the Doppler shifted signal is that this signal is composed of a multitude of frequencies. As a result of this, the PLL apparatus appears to jump from one frequency or another. Since, during operation, the PLL apparatus transiently locks onto the maximum frequency present in the signal giving an indication of the peaks of the envelope of peak frequencies in the Doppler shifted signal. If the difference voltage from the phase detector is averaged for some length of time by an integrator, the resulting signal gives an indication of the mean velocity. Whereas, the PLL technique does give some information concerning the blood flow, it does have definite limitations because of the complex nature of the Doppler shifted signal spectrum and the fact that the cardiac cycle is constantly varying.
The third method of analyzing the Doppler shifted signal is to do a Fourier transform spectrum analysis of the Doppler shift signal. The resulting output from the Fourier analysis is a signal which plots the power level of each particular frequency present in the signal against time. This method gives an indication of the instantaneous velocity patterns which occur during each individual cardiac cycle. This technique is described in Non-Invasive Clinical Measurements, J. P. Woodcock, London, Pittman Medical, 1977, Chapter 6, pp. 82-88, and utilization of this method is described in the papers by Y. Langlois, J. O. Roderer, A. Chang, D. J. Phillips, K. W. Beach, D. Martin, T. M. Chikos, and D. E. Strandness, Jr., "Evaluating Carotid Artery Disease--The Concordance Between Post Doppler/Spectrum Analysis and Angiography," Ultrasound in Medicine and Biology, Vol. 9, No. 1, pp. 51-63, 1983; and R. W. Barnes, S. E. Rittgers, W. W. Putney, "Real Time Doppler Spectrum Analysis--Predictive Value in Defining Operable Carotid Artery Disease," Archives of Surgery, Vol. 117, pp. 52-57, January, 1982.
Whereas, the Fourier analysis of the Doppler shift signal gives an indication of the energy at each of the Fourier harmonics of the waveform, the technique does suffer from certain problems. The primary problem of using the latter analysis of the Doppler shifted signal is that the Fourier analysis is based on the premise that the frequency components can have any relationship to each other including an extremely close relationship between the different frequencies. Because of this basic assumption, the Fourier analysis attempts to find harmonics to describe a complex signal in which the frequency components are close in phase and frequency. The problem with this assumption with respect to Doppler shifted signals resulting from blood flow is that the latter comprise only a few frequency components that are reasonably well spaced from each other in frequency.
Since the assumption of the Fourier analysis is that the signal is far more complex than it actually is, the resulting display from a Fourier analysis of the Doppler shifted signal tends to be extremely complicated, thus making visual representation difficult. This complex visual representation is further complicated by the fact that the cardiac cycle is varying making diagnosis difficult because the display is changing in a very complex manner.
Another problem that exists with utilizing Fourier analysis is that this type of analysis is very sensitive to the starting point of the signal under analysis. This factor comes into effect when an attempt is made to average the results from a number of Fourier analyses of individual cardiac cycles. Averaging is desirable to obtain accurate information. Techniques such as those described in the previously mentioned article by Langlois, et al., in which an EKG signal is used to indicate a relative starting point for the cycle still suffer from this problem since the precise starting point must be repetitively determined for the Fourier analysis technique. This is also complicated by the fact that the length of the cardiac cycles and the amount of blood flowing in these cycles varies with time. This further complicates the Fourier analysis by making it difficult to average the results of the cycle and also because when the results of the Fourier analysis are displayed, the resulting display appears quite different for different lengths of the cardiac cycle.
Another problem with the utilization of Fourier transform spectrum analysis of the Doppler shift signal is the relative cost of the equipment to do Fourier analysis. The additional cost of the instrumentation when the Fourier analysis circuitry is added, approximately increases the basic cost by four times. The additional cost for Fourier analysis is due to the fact that this analysis requires extremely intense mathematical calculations.
From the previous paragraphs it can be seen that there exists a need for an analysis technique which more closely models the fundamental nature of the Doppler shift signals and which also can be provided at a greatly reduced cost than the existing analysis techniques. In addition, there exists a need for a method of analysis that both accurately portrays the spectrum and allows the results of the spectrum analysis to be averaged over a number of cycles without introducing erroneous data in the results. In addition, there is a need for an analysis technique that presents to medical personnel a display which in a simple visual representation provides them with fundamental information on whether the blood flow is normal or abnormal.